Radiation Induced Late Damage to the Barrier Function of Small Blood Vessels in Mouse Bladder

Abstract

We identified changes in vascular barrier function in relation to collagen deposition during the late radiation response of mouse bladders. In this study albumin leakage was assessed as a marker of blood vessel barrier disruption. Female C3H/Neu mice were irradiated with a single dose of 20 Gy and sacrificed for (immuno) histological studies after 90, 120, 180, 240 and 360 days. The fractional area of subepithelial tissue with extravascular albumin signal was defined. Moreover, the amount of collagen was determined after Masson's trichrome staining on an arbitrary score of 0 to 3. Subepithelial albumin infiltration due to leakage from the blood vessels was seen in irradiated animals during the entire late phase. It was most pronounced at days 120 and 180 after treatment (vs control p <0.0001). Similarly an increase in collagen deposition in the bladder wall was seen during the whole late radiation phase but with increasing values toward the end of the experiment (day 360 vs control p <0.0001). Irradiation of the bladder results in late damage to the barrier function of small subepithelial blood vessels, causing pronounced albumin leakage at the early steps of the chronic radiation reaction, clearly preceding excessive collagen deposition in the bladder wall. Current data suggest a vascular component in the development of late radiation induced changes in the bladder.